Olfactory information is encoded in a combinatorial fashion by olfactory bulb glomeruli, which individually represent distinct chemical features of different odorants. This information is transmitted to the piriform cortex, where it is presumed to form combinations of these discrete signals, and leads to an odor percept. The focus of this proposal is to understand how cells in piriform cortex integrate information from olfactory bulb. I will attempt to gain fundamental insights into how olfactory information is represented in the brain by asking specific questions about the integrative properties of piriform cortex neurons. The experiments proposed here will determine the number of glomerular inputs onto single cells in piriform cortex (Aim 1). I will determine how many glomeruli are required to activate a single piriform cortex neuron and how combinations of coactive inputs from different glomeruli are integrated in piriform cortex neurons (Aim 2). I will also determine how higher brain areas affect the integration properties of piriform cortex neurons. I will specifically ask whether inputs onto piriform cortex neurons from orbitofrontal cortex alter the impact of sensory inputs from the bulb (Aim 3). These experiments will require the use of new techniques that will be developed during the mentored phase and used extensively during both the mentored and independent phases of the award. These data will shed light on the anatomical and physiological strategies employed by central neural circuits to process sensory stimuli. Such information is essential to understanding both the normal and pathological states of the central nervous system. The mentored phase of this award will take place in the laboratories of Dr. Richard Axel and Dr. Steven Siegelbaum at Columbia University. Dr. Axel has extensively studied the molecular, cellular and circuit-level basis for olfaction. Dr. Siegelbaum has made key discoveries illustrating how regulation and expression of ion channels affect neural circuits and alter behavior. Both Dr. Axel and Dr. Siegelbaum have distinguished track records in mentoring fellows through the transition to independence. RELEVANCE (See instructions): The central olfactory system is one of the most tractable brain circuits, permitting fundamental insights into how the brain processes sensory information. A clear understanding of these processes is crucial for an understanding of brain function in health and disease. For example, problems with odor perception are early indicators for serious neurological diseases, including Parkinson's and Alzheimers'Disease.